Hydrogel-Nanoparticles Composite System for Controlled Drug Delivery (original) (raw)
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Tunable hydrogel—Nanoparticles release system for sustained combination therapies in the spinal cord
Colloids and Surfaces B: Biointerfaces, 2013
Poly(methyl methacrylate) (PMMA) nanoparticles (NPs) were prepared by emulsion free radical polymerization. NPs with controlled dimension, as monitored by dynamic light scattering (DLS) and transmission electron microscopy (TEM), were produced by changing experimental parameters, such as the amount of emulsifier and the monomer feeding mode (batch or semi-batch). Then, different sized NPs (60, 80 and 130 nm) were loaded in polysaccharide-polyacrylic acid based hydrogels, cross-linked by covalent ester bonds between polyacrylic acid (PAA) and agarose chains, with different pore sizes (30, 60, 90 nm). The characteristics of the resulting composite hydrogel-NPs system were firstly studied in terms of rheological properties and ability to release Rhodamine B that presents steric hindrance similar to many neuroprotective agents used in spinal cord injury (SCI) repair. Then, diffusion-controlled release of different sized NPs from different entangled hydrogels was investigated in vitro and correlated with NPs diameter and hydrogel mean mesh size, showing different hindrances to the diffusion pathways. Release experiments and diffusion studies, rationalized by mathematical modeling and verified in vivo, allowed to build a material library able to satisfy different medical drug delivery needs.
Water-in-Water Emulsion Based Synthesis of Hydrogel Nanospheres with Tunable Release Kinetics
JOM, 2016
Poly(ethylene glycol) (PEG) micro/nanospheres have several unique advantages as polymer based drug delivery systems (DDS) such as tunable size, large surface area to volume ratio, and colloidal stability. Emulsification is one of the widely used methods for facile synthesis of micro/nanospheres. Twophase aqueous system based on polymer-polymer immiscibility is a novel approach for preparation of water-in-water (w/w) emulsions. This method is promising for the synthesis of PEG micro/nanospheres for biological systems, since the emulsion is aqueous and do not require organic solvents or surfactants. Here, we report the synthesis of nano-scale PEG hydrogel particles using w/w emulsions using phase separation of dextran and PEG prepolymer. Dynamic light scattering (DLS) and scaning electron microscopy (SEM) results demonstrated that nano-scale hydrogel spheres could be obtained with this approach. We investigated the release kinetics of a model drug, pregabalin (PGB) from PEG nanospheres and demonstrated the influence of polymerization conditions on loading and release of the drug as well as the morphology and size distribution of PEG nanospheres. The experimental drug release data was fitted to a stretched exponential function which suggested high correlation with experimental results to predict half-time and drug release rates from the model equation. The biocompatibility of nanospheres on human dermal fibroblasts using cell-survival assay suggested that PEG nanospheres with altered concentrations are non-toxic, and can be considered for controlled drug/molecule delivery.
Controlled drug release from hydrogel nanoparticle networks
Journal of Controlled Release, 2004
Monodisperse nanoparticles of poly-N-isopropylacrylamide-co-allylamine (PNIPAM-co-allylamine) and PNIPAM-coacrylic acid (PNIPAM-co-AA) were synthesized. The close-packed PNIPAM-co-allylamine and PNIPAM-co-AA nanoparticles were converted to three-dimensional gel networks by covalently crosslinking neighboring particles at room temperature and neutral pH using glutaric dialdehyde and adipic acid dihydrazide, respectively. Controlled release studies were conducted using dextran markers of various molecular weights as model macromolecular drugs. Release was quantified under various physical conditions, including a range of temperatures and dextran molecular weights. Dextran, entrapped in cavities in the nanoparticle network, was released with a rate regulated by their molecular weights and cavity size. No release from a conventional bulk PNIPAM gel, with high crosslinking density, was observed. The rate of release from the PNIPAM-co-allylamine network was temperature-dependant, being much faster at room temperature than that at human body temperature. In contrast, release of low molecular weight dextrans from the PNIPAM-co-AA network showed a temperature-independent release profile. These nanoparticle networks have several advantages over conventional bulk gels for controlling the release of high molecular weight biomolecules. D
Macromolecular Bioscience, 2006
Summary: Photocrosslinked nanogels with a hydrophobic core and hydrophilic shell are successfully fabricated with the goal of obtaining a biocompatible and biodegradable drug carrier for hydrophobic anticancer drugs. These nanogels are composed of amphiphilic triblock copolymers, poly(D,L‐lactic acid)/poly(ethylene glycol)/poly(D,L‐lactic acid) (PLA‐PEG‐PLA), with acrylated groups at the end of the PLA segments. The copolymers are synthesized by ring‐opening polymerization and possess a low CMC (49.6 mg · L−1), which easily helps to form micelles by self‐assembly. The acrylated end groups allow the micelles to be photocrosslinked by ultraviolet irradiation, which turn the micelles into nanogels. These nanogels exhibit excellent stability as a suspension in aqueous media at ambient temperature as compared to the micelles. Moreover, the size of the nanogels is easily manipulated in a range of 150 to 250 nm by changing the concentration of crosslinkers, e.g., ethylene glycol dimethacry...
Basic concepts and recent advances in nanogels as carriers for medical applications
Drug delivery, 2017
Nanogels in biomedical field are promising and innovative materials as dispersions of hydrogel nanoparticles based on crosslinked polymeric networks that have been called as next generation drug delivery systems due to their relatively high drug encapsulation capacity, uniformity, tunable size, ease of preparation, minimal toxicity, stability in the presence of serum, and stimuli responsiveness. Nanogels show a great potential in chemotherapy, diagnosis, organ targeting and delivery of bioactive substances. The main subjects reviewed in this article concentrates on: (i) Nanogel assimilation in the nanomedicine domain; (ii) Features and advantages of nanogels, the main characteristics, such as: swelling capacity, stimuli sensitivity, the great surface area, functionalization, bioconjugation and encapsulation of bioactive substances, which are taken into account in designing the structures according to the application; some data on the advantages and limitations of the preparation tec...
Hydrogels in controlled drug delivery systems
Iran Polym J, 2009
H ydrogels are a unique class of macromolecular networks that can hold a large fraction of an aqueous solvent within their structures. They are particularly suitable for biomedical applications, including controlled drug delivery, because of their ability to simulate biological tissues. Many hydrogel-based networks have been designed and fabricated to meet the needs of pharmaceutical and medical fields. The objective of this paper is to give a brief review on the fundamentals and recent advances in the design of hydrogel-based drug delivery systems (DDS) as well as the description of the release mechanism of bioactive molecules from these hydrogels. The structure and classification of hydrogels, swelling behaviour of hydrogels, different mechanisms of solvent diffusion into and drug release from hydrogels and mathematical description of these phenomena are elucidated. The most important properties of hydrogels relevant to their biomedical applications are also identified, especially for use of hydrogels as drug delivery systems. Kinetics of drug release from hydrogels A r c h i v e o f S I D
Nanogel-Integrated pH-Responsive Composite Hydrogels for Controlled Drug Delivery
ACS Biomaterials Science & Engineering, 2017
A novel pH-sensitive hydrogel system consisting of poly(methacrylic acid-g-ethylene glycol) (P(MAA-g-EG)) and acryloyl group modified-cholesterol-bearing pullulan (CHPOA) nanogels was developed for the controlled delivery of an anticonvulsant drug, pregabalin (PGB). Here, the hydrophilic hydrogel network provides the pH-sensitive swelling behavior, whereas nanogel components form separate reservoirs for the delivery of drugs with different hydro-phobicities. These nanocarrier-integrated hybrid gels were synthesized through both surface-initiated and bulk photo-polymerization approaches. The swelling and drug release behavior of these pH-responsive hydrogels synthesized by different photopolymerization approaches at visible and UV light wavelenghts were studied at acidic and basic pH values. Nanogel-integrated hydrogels exhibited higher swelling behavior compared to plain hydrogels in reversible swelling experiments. Similarly, the presence of nanogels in hydrogel network enhanced the loading and release percentages of PGB and the release was analyzed to describe the mode of transport through the network. In vitro cytotoxicity assay suggests that hydrogels in altered groups are nontoxic. This is the first report about the visible light-induced synthesis of a pH-responsive network incorporated CHPOA nanogels. Responsive and multifunctional properties of this system could be used for pH-triggered release of therapeutic molecules for clinical applications.
Nanogels: An Overview of Properties, Pharmaceutical Applications and Drug Loading Technique
2020
A nanoparticle which is composed of a hydrogel with a cross linked hydrophilic polymer network is known as “Nanogel”. The term nanogels defined as the nanosized particles formed by physically or chemically cross-linked polymer networks that is swell in a good solvent. The term “Nanogel” was first introduced to define cross-linked bifunctional networks of a polyion and a nonionic polymer for delivery of polynucleotides (cross-linked polyethyleneimine (PEI) and poly (ethylene glycol) (PEG) or PEG-cl-PEI). Nanogels based materials have high drug loading capacity, biocompatibility, and biodegradability which are the key points to design a drug delivery system effectively. Sudden outbreak in the field of nanotechnology have introduced the need for developing nanogel systems which proven their potential to deliver drugs in controlled, sustained and targetable manner. With the emerging field of polymer sciences it has now become inevitable to prepare smart nano-systems which can prove effe...
Polymeric Biomaterial Based Hydrogels for Biomedical Applications
Journal of Biomaterials and Nanobiotechnology, 2011
The paper describes the synthesis of pH sensitive interpenetrating polymeric network (IPN) beads composed of chitosan, glycine, glutamic acid, cross linked with glutaraldehyde and their use for controlled drug release. The drug was loaded into beads by varying their composition such as, amount of crosslinker glutaraldehyde, ratio of chitosan, glycine and glutamic acid. The beads were characterized by fourier transform infrared (FTIR) spectroscopy to confirm the cross linking reaction and drug interaction with crosslinked polymer in beads, Scanning Electron Microscopy (SEM) to understand the surface morphology and Differential scanning calorimetry (DSC) to find out the thermal stability of beads. X-Ray Diffraction (XRD) investigation was carried out to determine the crystalline nature of drug after loading into chitosan-glycine-glutamic acid IPN beads. Results indicated amorphous dispersion of chlorpheniramine maleate (CPM) in the polymeric matrix. The swelling behavior of the beads at different time intervals was monitored in solutions of pH 2.0 and pH 7.4. The release experiments were performed in solutions of pH 2.0 and pH 7.4 at 37˚C using chlorpheniramine maleate (CPM) as a model drug. The swelling behavior and release of drug were observed to be dependent on pH, degree of cross linking and their composition. The results indicate that the cross linked IPN beads of chitosan-glycine-glutamic acid might be useful as a vehicle for controlled release of drug. The kinetics of drug release from beads was best fitted by Higuchi's model in which release rate is largely governed by rate of diffusion through the matrix.